Charcot-Marie-Tooth disease (CMTD) is the most common inherited peripheral neuropathy, characterized by a progressive muscular atrophy that primarily affects the distal muscles. The underlying genetic causes for CMTD are unknown. CMTD displays all types of Mendelian patterns of inheritance. Linkage analysis has suggested at least two genetic loci for autosomal dominant CMTD, a disease characterized clinically by distal muscle wasting, pes cavus, hypertrophied peripheral nerves, absent deep tendon reflexes and slow nerve conduction velocity. This is referred to as hereditary motor and Duffy blood group locus on chromosome 1 (HMSNIB) while the location of the other form one large French Acadian pedigree and two other pedigrees. Linkage studies will be conducted in two large HMSNI pedigress using restriction fragment length polymorphism analysis with highly polymorphic DNA probes, to further localize the gene(s) for HMSNI by systematically excluding or including areas of the genome. Preliminary results have virtually excluded genetic and recombinant DNA techniques will be used to identify probes showing tighter linkage to the disease. These probes will be tested for linkage in other banked HMSNI pedigrees. Genetic linkage analysis will provide a method for clarifying the various subtyped of hereditary neuropathy. It should allow a better assessment of non-allelic heterogeneity in this disorder and may have an impact on presymptomatic and prenatal diagnosis.